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孕期母体暴露于拉莫三嗪对胎鼠性腺毒性的影响。

Effects of Maternal Exposure to Lamotrigine during Pregnancy on Gonadal Toxicity in Fetus Rats.

作者信息

Aryan Hoda, Movassaghi Shabnam, Ghasemi Amir, Darabi Roksana

机构信息

Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Iran.

Anatomy Department, Islamic Azad University, Tehran Medical Sciences, Tehran, Iran.

出版信息

Galen Med J. 2020 Oct 3;9:e1557. doi: 10.31661/gmj.v9i0.1557. eCollection 2020.

DOI:10.31661/gmj.v9i0.1557
PMID:34466552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8343942/
Abstract

BACKGROUND

Lamotrigine is one of the newest antiepileptic drugs that is used as one of the most common treatments in pregnancy. Since the investigation of the teratogenic effects of lamotrigine is very limited and there is no report of its teratogenic effects on fetal gonads, we aimed to investigate the teratogenic effects of lamotrigine on embryonic gonads.

MATERIALS AND METHODS

This study was performed on nine female Wistar female rats (8 weeks, weighing 180-200 mg). At first, the animals were inspected regularly by the preparation of vaginal smear and in the estrus phase in separate cages of mating, and after observing the vaginal plaque, were randomly divided into three groups (n=3). Control group did not receive any treatment. In the lamotrigine group (20mg/kg), and the vehicle group (same volume of normal saline) were injected intraperitoneally from days 8 to 13 of pregnancy. On day 20, animals were anesthetized by sodium pentobarbital (40 mg/kg), and embryos were extracted through laparotomy. First, fetuses were weighed, and their height (crown-rump length) was measured. Then the gonads of the fetuses were removed and, stained with H & E, and examined by optical microscope.

RESULTS

Our results showed that in the lamotrigine group, the number of seminiferous tubules and Sertoli cells in the male embryos and the number of oocytes in the female embryos decreased significantly compared to the control and vehicle groups (P≤0.05).

CONCLUSION

The results of this study showed that treatment with 20 mg/kg lamotrigine in mothers during pregnancy could cause damage to fetal gonads.

摘要

背景

拉莫三嗪是最新的抗癫痫药物之一,是孕期最常用的治疗药物之一。由于对拉莫三嗪致畸作用的研究非常有限,且尚无其对胎儿性腺致畸作用的报道,我们旨在研究拉莫三嗪对胚胎性腺的致畸作用。

材料与方法

本研究对9只雌性Wistar大鼠(8周龄,体重180 - 200毫克)进行。首先,通过制备阴道涂片定期检查动物,并在发情期将其置于单独的交配笼中,观察到阴道斑后,将其随机分为三组(n = 3)。对照组不接受任何治疗。拉莫三嗪组(20毫克/千克)和赋形剂组(相同体积的生理盐水)在妊娠第8天至13天腹腔注射。在第20天,用戊巴比妥钠(40毫克/千克)麻醉动物,通过剖腹术取出胚胎。首先,称取胎儿体重,测量其身高(顶臀长度)。然后取出胎儿的性腺,用苏木精和伊红染色,并用光学显微镜检查。

结果

我们的结果显示,与对照组和赋形剂组相比,拉莫三嗪组雄性胚胎的生精小管和支持细胞数量以及雌性胚胎的卵母细胞数量显著减少(P≤0.05)。

结论

本研究结果表明,孕期母亲使用20毫克/千克拉莫三嗪治疗可能会对胎儿性腺造成损害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/83df4b904507/gmj-9-e1557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/31a124458831/gmj-9-e1557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/130833f0b1ed/gmj-9-e1557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/c2f1cdc86452/gmj-9-e1557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/83df4b904507/gmj-9-e1557-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/31a124458831/gmj-9-e1557-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/130833f0b1ed/gmj-9-e1557-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/c2f1cdc86452/gmj-9-e1557-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/634d/8343942/83df4b904507/gmj-9-e1557-g004.jpg

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本文引用的文献

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Maternal Carbamazepine Therapy and Unusual Adverse Effects in a Breastfed Infant.母亲服用卡马西平治疗及其对母乳喂养婴儿的异常不良反应
Breastfeed Med. 2018 Mar;13(2):155-157. doi: 10.1089/bfm.2017.0235. Epub 2018 Feb 12.
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Maternal and Fetal Outcomes After Lamotrigine Use in Pregnancy: A Retrospective Analysis from an Urban Maternal Mental Health Centre in New Zealand.妊娠期间使用拉莫三嗪后的母婴结局:来自新西兰一家城市孕产妇心理健康中心的回顾性分析
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Prenatal exposure to lamotrigine: effects on postnatal development and behaviour in rat offspring.
孕期暴露于拉莫三嗪:对大鼠后代出生后发育及行为的影响。
ISRN Neurosci. 2014 Apr 14;2014:163459. doi: 10.1155/2014/163459. eCollection 2014.
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Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?与其他畸形相比,孕期使用拉莫三嗪会增加口面部裂隙的风险吗?
Neurology. 2008 Sep 2;71(10):714-22. doi: 10.1212/01.wnl.0000316194.98475.d8. Epub 2008 Jul 23.
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The effect of Vigabatrin, Lamotrigine and Gabapentin on the fertility, weights, sex hormones and biochemical profiles of male rats.氨己烯酸、拉莫三嗪和加巴喷丁对雄性大鼠生育能力、体重、性激素及生化指标的影响。
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Gonadal morphology and sex hormones in male and female Wistar rats after long-term lamotrigine treatment.长期服用拉莫三嗪后雄性和雌性Wistar大鼠的性腺形态及性激素变化
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